X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world

Zeinab A El-Sayed, Irina Abramova, Juan Carlos Aldave, Waleed Al-Herz, Liliana Bezrodnik, Rachida Boukari, Ahmed Aziz Bousfiha, Caterina Cancrini, Antonio Condino-Neto, Ghassan Dbaibo, Beata Derfalvi, Figen Dogu, J David M Edgar, Brian Eley, Rasha Hasan El-Owaidy, Sara Elva Espinosa-Padilla, Nermeen Galal, Filomeen Haerynck, Rima Hanna-Wakim, Elham HossnyAydan Ikinciogullari, Ebtihal Kamal, Hirokazu Kanegane, Nadia Kechout, Yu Lung Lau, Tomohiro Morio, Viviana Moschese, Joao Farela Neves, Monia Ouederni, Roberto Paganelli, Kenneth Paris, Claudio Pignata, Alessandro Plebani, Farah Naz Qamar, Sonia Qureshi, Nita Radhakrishnan, Nima Rezaei, Nelson Rosario, John Routes, Berta Sanchez, Anna Sediva, Mikko Rj Seppanen, Edith Gonzalez Serrano, Anna Shcherbina, Surjit Singh, Sangeetha Siniah, Guiseppe Spadaro, Mimi Tang, Ana Maria Vinet, Alla Volokha, Kathleen E Sullivan

Research output: Contribution to journalArticle

Abstract

Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features.

Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.

Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians.

Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.

Original languageEnglish
Pages (from-to)100018
JournalWorld Allergy Organization Journal
Volume12
Issue number3
DOIs
Publication statusPublished - 2019

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Phenotype
Poliomyelitis
Physicians
Therapeutics
Morbidity
Patient Education
Mycobacterium
Bruton type agammaglobulinemia
Inflammatory Bowel Diseases
Practice Guidelines
Lung Diseases
Immunoglobulins
Vaccination
Chronic Disease
Vaccines
Lymphocytes
Education
Survival
Mortality
Infection

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El-Sayed, Z. A., Abramova, I., Aldave, J. C., Al-Herz, W., Bezrodnik, L., Boukari, R., ... Sullivan, K. E. (2019). X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world. World Allergy Organization Journal, 12(3), 100018. https://doi.org/10.1016/j.waojou.2019.100018

X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world. / El-Sayed, Zeinab A; Abramova, Irina; Aldave, Juan Carlos; Al-Herz, Waleed; Bezrodnik, Liliana; Boukari, Rachida; Bousfiha, Ahmed Aziz; Cancrini, Caterina; Condino-Neto, Antonio; Dbaibo, Ghassan; Derfalvi, Beata; Dogu, Figen; Edgar, J David M; Eley, Brian; El-Owaidy, Rasha Hasan; Espinosa-Padilla, Sara Elva; Galal, Nermeen; Haerynck, Filomeen; Hanna-Wakim, Rima; Hossny, Elham; Ikinciogullari, Aydan; Kamal, Ebtihal; Kanegane, Hirokazu; Kechout, Nadia; Lau, Yu Lung; Morio, Tomohiro; Moschese, Viviana; Neves, Joao Farela; Ouederni, Monia; Paganelli, Roberto; Paris, Kenneth; Pignata, Claudio; Plebani, Alessandro; Qamar, Farah Naz; Qureshi, Sonia; Radhakrishnan, Nita; Rezaei, Nima; Rosario, Nelson; Routes, John; Sanchez, Berta; Sediva, Anna; Seppanen, Mikko Rj; Serrano, Edith Gonzalez; Shcherbina, Anna; Singh, Surjit; Siniah, Sangeetha; Spadaro, Guiseppe; Tang, Mimi; Vinet, Ana Maria; Volokha, Alla; Sullivan, Kathleen E.

In: World Allergy Organization Journal, Vol. 12, No. 3, 2019, p. 100018.

Research output: Contribution to journalArticle

El-Sayed, ZA, Abramova, I, Aldave, JC, Al-Herz, W, Bezrodnik, L, Boukari, R, Bousfiha, AA, Cancrini, C, Condino-Neto, A, Dbaibo, G, Derfalvi, B, Dogu, F, Edgar, JDM, Eley, B, El-Owaidy, RH, Espinosa-Padilla, SE, Galal, N, Haerynck, F, Hanna-Wakim, R, Hossny, E, Ikinciogullari, A, Kamal, E, Kanegane, H, Kechout, N, Lau, YL, Morio, T, Moschese, V, Neves, JF, Ouederni, M, Paganelli, R, Paris, K, Pignata, C, Plebani, A, Qamar, FN, Qureshi, S, Radhakrishnan, N, Rezaei, N, Rosario, N, Routes, J, Sanchez, B, Sediva, A, Seppanen, MR, Serrano, EG, Shcherbina, A, Singh, S, Siniah, S, Spadaro, G, Tang, M, Vinet, AM, Volokha, A & Sullivan, KE 2019, 'X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world', World Allergy Organization Journal, vol. 12, no. 3, pp. 100018. https://doi.org/10.1016/j.waojou.2019.100018
El-Sayed, Zeinab A ; Abramova, Irina ; Aldave, Juan Carlos ; Al-Herz, Waleed ; Bezrodnik, Liliana ; Boukari, Rachida ; Bousfiha, Ahmed Aziz ; Cancrini, Caterina ; Condino-Neto, Antonio ; Dbaibo, Ghassan ; Derfalvi, Beata ; Dogu, Figen ; Edgar, J David M ; Eley, Brian ; El-Owaidy, Rasha Hasan ; Espinosa-Padilla, Sara Elva ; Galal, Nermeen ; Haerynck, Filomeen ; Hanna-Wakim, Rima ; Hossny, Elham ; Ikinciogullari, Aydan ; Kamal, Ebtihal ; Kanegane, Hirokazu ; Kechout, Nadia ; Lau, Yu Lung ; Morio, Tomohiro ; Moschese, Viviana ; Neves, Joao Farela ; Ouederni, Monia ; Paganelli, Roberto ; Paris, Kenneth ; Pignata, Claudio ; Plebani, Alessandro ; Qamar, Farah Naz ; Qureshi, Sonia ; Radhakrishnan, Nita ; Rezaei, Nima ; Rosario, Nelson ; Routes, John ; Sanchez, Berta ; Sediva, Anna ; Seppanen, Mikko Rj ; Serrano, Edith Gonzalez ; Shcherbina, Anna ; Singh, Surjit ; Siniah, Sangeetha ; Spadaro, Guiseppe ; Tang, Mimi ; Vinet, Ana Maria ; Volokha, Alla ; Sullivan, Kathleen E. / X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world. In: World Allergy Organization Journal. 2019 ; Vol. 12, No. 3. pp. 100018.
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title = "X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world",
abstract = "Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features.Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34{\%} of patients and the lack of genetic studies in 39{\%} of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41{\%} of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3{\%} of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22{\%}) and reached above 70{\%} in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16{\%}) and reflected the ongoing need for education of both patients and referring physicians.Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.",
author = "El-Sayed, {Zeinab A} and Irina Abramova and Aldave, {Juan Carlos} and Waleed Al-Herz and Liliana Bezrodnik and Rachida Boukari and Bousfiha, {Ahmed Aziz} and Caterina Cancrini and Antonio Condino-Neto and Ghassan Dbaibo and Beata Derfalvi and Figen Dogu and Edgar, {J David M} and Brian Eley and El-Owaidy, {Rasha Hasan} and Espinosa-Padilla, {Sara Elva} and Nermeen Galal and Filomeen Haerynck and Rima Hanna-Wakim and Elham Hossny and Aydan Ikinciogullari and Ebtihal Kamal and Hirokazu Kanegane and Nadia Kechout and Lau, {Yu Lung} and Tomohiro Morio and Viviana Moschese and Neves, {Joao Farela} and Monia Ouederni and Roberto Paganelli and Kenneth Paris and Claudio Pignata and Alessandro Plebani and Qamar, {Farah Naz} and Sonia Qureshi and Nita Radhakrishnan and Nima Rezaei and Nelson Rosario and John Routes and Berta Sanchez and Anna Sediva and Seppanen, {Mikko Rj} and Serrano, {Edith Gonzalez} and Anna Shcherbina and Surjit Singh and Sangeetha Siniah and Guiseppe Spadaro and Mimi Tang and Vinet, {Ana Maria} and Alla Volokha and Sullivan, {Kathleen E}",
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TY - JOUR

T1 - X-linked agammaglobulinemia (XLA):Phenotype, diagnosis, and therapeutic challenges around the world

AU - El-Sayed, Zeinab A

AU - Abramova, Irina

AU - Aldave, Juan Carlos

AU - Al-Herz, Waleed

AU - Bezrodnik, Liliana

AU - Boukari, Rachida

AU - Bousfiha, Ahmed Aziz

AU - Cancrini, Caterina

AU - Condino-Neto, Antonio

AU - Dbaibo, Ghassan

AU - Derfalvi, Beata

AU - Dogu, Figen

AU - Edgar, J David M

AU - Eley, Brian

AU - El-Owaidy, Rasha Hasan

AU - Espinosa-Padilla, Sara Elva

AU - Galal, Nermeen

AU - Haerynck, Filomeen

AU - Hanna-Wakim, Rima

AU - Hossny, Elham

AU - Ikinciogullari, Aydan

AU - Kamal, Ebtihal

AU - Kanegane, Hirokazu

AU - Kechout, Nadia

AU - Lau, Yu Lung

AU - Morio, Tomohiro

AU - Moschese, Viviana

AU - Neves, Joao Farela

AU - Ouederni, Monia

AU - Paganelli, Roberto

AU - Paris, Kenneth

AU - Pignata, Claudio

AU - Plebani, Alessandro

AU - Qamar, Farah Naz

AU - Qureshi, Sonia

AU - Radhakrishnan, Nita

AU - Rezaei, Nima

AU - Rosario, Nelson

AU - Routes, John

AU - Sanchez, Berta

AU - Sediva, Anna

AU - Seppanen, Mikko Rj

AU - Serrano, Edith Gonzalez

AU - Shcherbina, Anna

AU - Singh, Surjit

AU - Siniah, Sangeetha

AU - Spadaro, Guiseppe

AU - Tang, Mimi

AU - Vinet, Ana Maria

AU - Volokha, Alla

AU - Sullivan, Kathleen E

PY - 2019

Y1 - 2019

N2 - Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features.Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians.Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.

AB - Background: X-linked agammaglobulinemia is an inherited immunodeficiency recognized since 1952. In spite of seven decades of experience, there is still a limited understanding of regional differences in presentation and complications. This study was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to better understand regional needs, challenges and unique patient features.Methods: A survey instrument was designed by the Primary Immunodeficiencies Committee of the World Allergy Organization to collect both structured and semi-structured data on X-linked agammaglobulinemia. The survey was sent to 54 centers around the world chosen on the basis of World Allergy Organization participation and/or registration in the European Society for Immunodeficiencies. There were 40 centers that responded, comprising 32 countries.Results: This study reports on 783 patients from 40 centers around the world. Problems with diagnosis are highlighted by the reported delays in diagnosis>24 months in 34% of patients and the lack of genetic studies in 39% of centers Two infections exhibited regional variation. Vaccine-associated paralytic poliomyelitis was seen only in countries with live polio vaccination and two centers reported mycobacteria. High rates of morbidity were reported. Acute and chronic lung diseases accounted for 41% of the deaths. Unusual complications such as inflammatory bowel disease and large granular lymphocyte disease, among others were specifically enumerated, and while individually uncommon, they were collectively seen in 20.3% of patients. These data suggest that a broad range of both inflammatory, infectious, and autoimmune conditions can occur in patients. The breadth of complications and lack of data on management subsequently appeared as a significant challenge reported by centers. Survival above 20 years of age was lowest in Africa (22%) and reached above 70% in Australia, Europe and the Americas. Centers were asked to report their challenges and responses (n = 116) emphasized the difficulties in access to immunoglobulin products (16%) and reflected the ongoing need for education of both patients and referring physicians.Conclusions: This is the largest study of patients with X-linked agammaglobulinemia and emphasizes the continued morbidity and mortality of XLA despite progress in diagnosis and treatment. It presents a world view of the successes and challenges for patients and physicians alike. A pivotal finding is the need for education of physicians regarding typical symptoms suggesting a possible diagnosis of X-linked agammaglobulinemia and sharing of best practices for the less common complications.

U2 - 10.1016/j.waojou.2019.100018

DO - 10.1016/j.waojou.2019.100018

M3 - Article

C2 - 30937141

VL - 12

SP - 100018

JO - World Allergy Organization Journal

JF - World Allergy Organization Journal

SN - 1939-4551

IS - 3

ER -